Treatment outcomes of acute appendicitis and associated factors among admitted patients with a diagnosis of acute abdomen in Debre Markos Referral Hospital, Amhara Region, North West Ethiopia

Introduction Appendicitis is an inflammation of the vermiform appendix and is one of the most common causes of an acute abdomen in young adults. If left untreated, it can lead to appendiceal abscess, perforation and peritonitis. Objective To assess treatment outcomes of acute appendicitis and associated factors among admitted patients with a diagnosis of acute abdomen. Methods and materials: A cross sectional study was employed among 169 patients using a census. Data were collected from patient medical records by using a checklist. Data were entered using Epi-data and analysed by statistical product and service solution. Logistic regression analysis was employed. Results Among 303 patients with a diagnosis of acute abdomen, 169 (55.7%) developed acute appendicitis; of whom, 45 (26.6%) developed unfavourable treatment outcomes. Patients who had elevated white blood cell count at the time of presentation (adjusted odds ratio = 4.7; 95% confidence interval (1.95, 11.35)) and intraoperative appendiceal abscess (adjusted odds ratio = 3.8; 95% confidence interval (1.61, 9.07)) were significantly associated with an unfavourable appendicitis treatment outcome. Conclusion and recommendation: Nearly a quarter of the patients developed unfavourable treatment outcomes. Elevated white blood cell count and intraoperative appendiceal abscess were significantly associated with unfavourable appendicitis treatment outcome. Therefore, early detection and treatment of appendiceal abscess is crucial for a better outcome.


Introduction
Acute abdomen is a condition of sudden severe abdominal pain, usually requiring emergency surgery, caused by acute diseases of or injury to internal organs. Common syptoms in patients with acute abdomen are abdominal pain, vomiting, abdominal distension and constipation. Acute appendicitis is one of the major causes of acute abdomen. Other causes of acute abdomen include cholelithiasis, intestinal obstruction, peptic ulcer perforation, acute pancreatitis and obstetric and gynaecological related diseases ( The appendix is an immunologic organ that participates in the secretion of immunoglobulin, such as immunoglobulin A. Appendicitis is defined as the inflammation of the vermiform (worm-shaped) appendix, a narrow blind ending pouch approximately 5-9cm long opening off the caecum. Acute appendicitis is the most common cause of an acute abdomen in young adults. Appendicitis is thought to result from obstruction of the appendiceal lumen, typically by lymphoid hyperplasia, but occasionally by a fecalith, foreign body or even worms. Obstruction of the lumen by fecalith or lymphoid tissue results in distension of the appendix, bacterial overgrowth, infection; venous and lymphatic congestion; ulceration and transmural spread of infection through the appendicular wall. The inflammation and infection may result in the thrombosis of blood vessels causing ischaemia, necrosis and perforation. If untreated, necrosis, gangrene and perforation occur. If the perforation is contained by the omentum, an appendiceal abscess results (Froggatt & Harmston 2011, Poon et al 2017, Williams & O'Connell 2013.
Appendectomy, which is the gold standard in the management of acute appendicitis, is the most frequently performed urgent abdominal operation and is often the first major procedure performed by a surgeon in training. Advances in modern radiographic imaging have improved diagnostic accuracy; however, the diagnosis of appendicitis remains essentially clinical, requiring a mixture of observation, clinical acumen and surgical science and as such it remains an enigmatic challenge and a reminder of the art of surgical diagnosis (Hobler 1998, Williams & O'Connell 2013.
Appendicitis can occur at any age but is most common in adolescents and young adults. It causes vague abdominal pain that starts at periumbilical area and progresses to right lower quadrant (RLQ) and is usually accompanied by low grade fever, loss of appetite, nausea and sometimes by vomiting. Similarly, the abdomen is tense, and the client usually flexes the right hip to relieve the discomfort. Generally, the location of the appendix may also influence the type of pain. For example, if the tip of the appendix is against the rectum, the client may experience pain with defecation. If the tip is near the bladder or against a ureter, the client may experience pain with urination and if the appendix perforates, more diffuse abdominal pain is experienced. The abdomen may also be distended secondary to paralytic ileus (Sellars & Boorman 2017, Timby & Smith 2013. The Alvarado score is the most widely used diagnostic aid for the diagnosis of appendicitis. The modified Alvarado scale assigns a score to each of the following diagnostic criteria: Migratory right iliac fossa pain (1 point), anorexia (1 point), nausea/vomiting (1 point), tenderness in the right iliac fossa (2 points), rebound tenderness in the right iliac fossa (1 point), fever >37.5 C (1 point) and leukocytosis (2 points). A low Alvarado score (<5) has more diagnostic utility to 'rule out' appendicitis than a high score (7) does to 'rule in' the diagnosis. The addition of this decision has the potential to improve specificity and lead to lower falsepositive rates in diagnosis of acute appendicitis, but decision aids cannot definitively determine or exclude the possibility of appendicitis (Liu et al 2006).
Extreme age, delay in presentation, stage or duration of acute appendicitis, intake of antibiotics outside health care institutions, presence of comorbid condition and immunologic status of the patient can affect treatment outcomes of acute appendicitis. Morbidity and mortality rates after surgical treatment of acute appendicitis are still a major challenge in developing world (Nouri et al 2017, Tsegaye et al 2007.
The commonly encountered complications in surgical practices related to acute appendicitis can present preoperatively like perforation which can lead to local or generalised peritonitis, appendiceal abscess and mass or postoperative complications such as superficial and deep wound infections and wound dehiscence, prolonged ileus, pneumonia, bowel obstruction and intra-abdominal abscesses (Andersson 2007, Bekele & Mekasha 2006. The diagnosis of acute appendicitis is generally made from clinical examination (history, physical examination), laboratory investigation and/or imaging devices (ultrasound, CT scan and MRI). However, there is limited access to high quality advanced imaging modalities (CT scan, MRI) in most settings in Ethiopia. Besides this, most surgeons in Ethiopia remove the appendix through an open incision in the right lower abdominal wall rather than laparoscopically in most settings. This further prolongs the patient's postoperative pain, hospital stay, and return to bowel function and normal activity. Therefore, assessing the treatment outcome and the factors associated with acute appendicitis is crucial.

Study design, area and period
Institutional based cross sectional study was employed among patients who have had appendectomy. The study was conducted by reviewing records from 2018 to 2019.
Sample size determination and sampling procedure All patients, who had operative management for acute appendicitis and were admitted from 2018 to 2019, were included in the study. However, patients with acute appendicitis who had incomplete data record over the variable of interest were excluded from the study. The sample size was determined by census sampling method, in which all acute appendicitis cases operated from 2018 to 2019 were included in the study giving a total sample size of 169 patients.

Study variables and operational definitions
The outcome variable of the study was treatment outcomes of acute appendicitis (favourable and unfavourable), whereas the predictor variables of the study were patient related variables (age, sex, residence), disease related variables (clinical sign and symptoms, duration of illness, intraoperative findings, preoperative WBC count and index of abdominal ultrasound) and treatment related variables (type of abdominal incision, procedure done, intake of preoperative antibiotics and length of hospital stay).
The following terms were described in such a way in this study.
Length of hospital stay: Number of days elapsed while the patient is in the hospital.
Outcome: Condition of the patient at discharge (either improved with no postoperative complication(s) or developed one or more complications).
Favourable outcome: If patients who underwent appendectomy for the clinical examination (history, physical examination), laboratory investigation and ultrasonographic diagnosis of acute appendicitis were improved and discharged from the hospital without developing postoperative complications following appendectomy.
Unfavourable outcome: Patients with a clinical examination (history, physical examination), laboratory investigation and ultra-sonographic diagnosis of acute appendicitis who developed one or more postoperative complication(s), e.g. wound infection, intraperitoneal fluid collection, pneumonia and death during intra or postoperative period.

Data collection procedure, quality assurance and analysis
Data were collected from patient medical records, registration books and anaesthesia charts available in the hospital by checklists using two trained data collectors who are both fourth year BSc nursing students. First, the medical record number for all the patients in the study period was identified from registration books (logbooks). Then their charts were retrieved from the card office and those tools including sociodemographic characteristics, signs and symptoms, physical findings, outcomes, complications encountered and other relevant items related to the disease were reviewed. Finally, data were summarised, analysed, interpreted and edited. The data were checked for completeness, cleaned, coded and entered into Epi-data version 4.2 and then analysed using statistical product and service solution version 25 statistical software. Bivariate and multivariable logistic regression models were used. Crude odds ratios with 95% confidence intervals were estimated in the bivariable logistic regression analysis to assess the association between each predictor variable and outcome variable. In the bivariable logistic regression, variables with P-value <0.2 were fitted into the multivariable logistic regression analysis. Finally, adjusted odds ratios with their 95% confidence intervals were estimated to assess the strength of association, and variables with P-value <0.05 were considered statistically significant factors. Model fitness was checked using Hosmer-Lemeshow goodness fit test, which was 0.6. Data quality was assured by training of data collectors, collecting and cross matching of patient charts and surgery registration logbooks before data collection, preparing checklists and supervising and assisting data collectors closely.

Sociodemographic characteristics
Out of all 303 patients admitted with a diagnosis of acute abdomen, 169 (55.7%) patients underwent operative management for a clinical diagnosis of acute appendicitis. Among those who underwent surgery with a clinical diagnosis of acute appendicitis and who fulfilled the eligibility criteria, 107 (63.3%) were males and 62 (36.7%) were females. Moreover, 69 (40.8%) of patients were urban and 100 (59.2%) were rural dwellers and their mean age was 24.6 � 11.8 SD years (Table 1).

Clinical symptoms
Abdominal pain was invariably the main presenting complaint of patients with acute appendicitis. Among

Factors affecting treatment outcomes of acute appendicitis
In bivariable logistic regression analysis, elevated WBC count, presence of intraoperative appendiceal abscess, peritonitis, temperature and duration of illness before reaching hospital were statistically associated with treatment outcome of acute appendicitis. However, only two variables were statistically associated with treatment outcome of acute appendicitis after adjusting for possible confounders. These were elevated WBC count at the time of presentation and intraoperative appendiceal abscess (Table 4). Patients who had elevated WBC count (>11,000cells/nl) at the time of presentation were 4.7 times more likely to develop unfavourable acute appendicitis treatment outcome as  compared to those who had no elevated, 4000-1100cells/nl, WBC count (AOR ¼ 4.7; 95% CI (1.95, 11.35)). Similarly, those patients who had an intraoperative appendiceal abscess were 3.8 times more likely to have unfavourable acute appendicitis treatment outcome as compared to their counterparts (AOR ¼ 3.8; 95% CI (1.61, 9.07)).

Discussion
In this study, nearly a quarter (26.6%) of the patients developed unfavourable treatment outcomes of acute appendicitis with postoperative complications. The most common unfavourable outcomes were wound infection, pneumonia, intraperitoneal fluid collection and death. This finding is lower than studies conducted in Kumasi, Ghana (43.1%) (Ohene-Yeboah & Togbe 2006) and Edendale Hospital in Pietermaritzburg, South Africa (44%) (Kong et al 2012). However, this study is comparable with a study carried out at Nottingham, UK that ranges from <5% in simple appendicitis to 20% in cases with perforation and gangrene (Humes & Simpson 2006). The possible explanation for the above discrepancy could be the difference in socioeconomic and organisational set-up among countries.
Elevated WBC count at the time of presentation and presence of intraoperative appendiceal abscess were the factors associated with treatment outcome of acute appendicitis in this study. Patients who had elevated WBC count (>11,000cells/nl) at the time of presentation were more likely to develop an unfavourable acute appendicitis treatment outcome as compared to those who had no elevated WBC count. This was supported by a study done in Kathmandu, Nepal (Subedi et al 2011). Similarly, those patients who had an intraoperative appendiceal abscess were more likely to develop unfavourable acute appendicitis treatment outcome as compared to their counterparts. The possible explanation might be due to the fact that the presence of contaminated surgical space leads to infection.
The most common intraoperative finding was an inflamed/phlegmonous appendix followed by a perforated appendix.  . This might be due to the inflammatory process at the appendix.
All patients who were diagnosed with acute appendicitis were given preoperative IV antibiotics. The most frequent type of abdominal incision was RLQ transverse incision followed by midline vertical incision. Moreover, the most common operative procedure done was appendectomy followed by appendectomy with abscess drainage.

Limitation of the study
Since the study depends on medical records, the study is prone to selection bias. A total of ten patients were excluded because of incomplete charts.

Conclusion
Among patients who underwent appendectomy for the treatment of acute appendicitis, nearly one-fourth of them developed unfavourable treatment outcomes. The most common unfavourable outcomes were wound infection, pneumonia, intraperitoneal fluid collection and death. Elevated WBC count at the time of presentation and presence of intraoperative appendiceal abscess were the factors associated with the unfavourable treatment outcome of acute appendicitis. The majority of patients developed acute appendicitis in the first and second decades of their life. In all patients, abdominal pain was invariably the main presenting complaint and the most common physical finding was RLQ tenderness.

Recommendation
Health care practitioners should investigate CBC for patients who had clinical symptoms of acute appendicitis for the presence of leukocytosis and left shift in the differential count that ultimately affects treatment outcomes of acute appendicitis.
Early detection of acute appendicitis before developing complications like appendiceal abscess is crucial for favourable outcomes of acute appendicitis treatment. Besides this, early appendectomy after confirmatory diagnosis of acute appendicitis is recommended especially for those having features of peritonitis, raised WBC count and delayed presentation to reduce the risk of developing unfavourable treatment outcomes.

Competing Interests
None declared.

Funding
We have not obtained any funding for this study.

Ethics approval
The study was conducted after obtaining official permission to undertake this study from Debre Markos University, College of Health Sciences Research and Ethical Review Committee. A support and permission letter were provided to Debre Markos Referral Hospital (DMRH). Staffs at the Card room, surgical ward and operation room were informed about the purpose of the study and verbal consent was obtained. Confidentiality of the patient's information was assured and the information was recorded anonymously.

Guarantor
Abebe Dilie Afenigus accepts official responsibility for the overall integrity of the manuscript (including ethics, data handling, reporting of results, and study conduct).

Contributorship
AD: conceived, designed the study, supervised the data collection, and performed the data analysis, interpretation of the result and drafting the manuscript. AM and BK participated in designed the study, data analysis and data interpretation, editing the manuscript. All authors read and approved the final manuscript.

Availability of data
All relevant data are within the paper and its supporting information files.